Reye's Syndrome is characterized by severe mitochondrial injury as determined by electron microscpoy of liver biopsies obtained from children in critical stages of illness. The goal of this project is to study possible causes of the mitochondrial damage. The study is based on the hypothesis that a substance deleterious to mitochondria might be detected in serum. Reye's patient serum will therefore be tested in several in vitro assays of mitochondrial function, including: citrulline synthesis, oxidative phosphorylation, fatty acid oxidation, and protein synthesis. If Reye's serum has effects different from those of normal serum, the active substance will be isolated and identified to determine a possible pathogenic role in this illness. In addition, the study of how normal mitochondrial function is regulated will continue in order to increase the potential for predicting the common denominator for the diverse metabolic abnormalities that characterize Reye's syndrome.